CN112955201A

CN112955201A - Reservoir for an inhalation device

Info

Publication number: CN112955201A
Application number: CN201980073594.XA
Authority: CN
Inventors: J·拉维特
Original assignee: Softhale NV
Current assignee: Invox Belgium NV
Priority date: 2018-11-09
Filing date: 2019-11-07
Publication date: 2021-06-11
Anticipated expiration: 2039-11-07
Also published as: US20220031969A1; WO2020094761A1; BR112021008861A2; TW202034976A; JP7422279B2; CA3116936A1; JP2022506180A; EP3877023A1; CN112955201B

Abstract

The present invention relates to the field of inhalation devices for medically active liquids. In particular, the invention relates to cartridges containing said liquid for use in such inhalation devices. Cartridge (1) for storing a medically active liquid (L) and for supplying it to a pumping unit of an inhalation device comprises an outer container (3) enclosing a collapsible inner bag (4) and a cap (5) capable of closing off the container (3), the cap (5) further providing an openable access opening (6) to the inner bag (4), wherein further the container (3) of the cartridge (1) has a pressure compensation opening (7), and wherein the pressure compensation opening (7) is located in an area (8) covered by the cap (5). In a method for providing pressure compensation to the interior of an outer container (3) of a cartridge (1) containing a collapsible inner bag, initially, the pressure compensation opening (7) is closed before the cartridge (1) is connected to a holder (2), and subsequently, when the cartridge (1) is connected to the holder (2), an air gap (9) is provided which allows pressure equalization of the interior of the containing bag from the ambient pressure by means of mechanically deforming (i) the area of the outer container (3) comprising the pressure compensation opening and/or (ii) the area of the cap (5) covering the pressure compensation opening.

Description

Reservoir for an inhalation device

Technical Field

The present invention relates to the field of inhalation devices for medically active liquids. In particular, the invention relates to cartridges containing said liquid for such inhalation devices.

Background

Nebulizers or other aerosol generators for liquids have been known in the art since a long time ago. Such devices are used in particular in medicine and therapy. There, they are used as inhalation devices for applying active ingredients in the form of aerosols (i.e. small droplets embedded in a gas). Such an inhalation device is known, for example, from document EP 0627230B 1. Typical components of such inhalation devices are: a housing that can be held in an operator's hand; a reservoir containing a liquid to be aerosolized and a holder for holding the cartridge; a pumping unit downstream of this reservoir for generating a pressure high enough to carry out the nebulization; means for storing potential energy connected to this pumping unit, such as a spring; and an atomizing device in the form of one or several nozzles downstream of this pumping unit.

By means of the pumping unit, liquid is drawn from the reservoir in discrete amounts, i.e. discontinuously, and fed to the nozzle. The pumping unit operates without propellant and generates pressure mechanically, preferably by being driven by the aforementioned spring.

Improvements to such inhalation devices are disclosed in patent application PCT/EP2018/061056 filed by the same applicant as the present invention, the content of which is incorporated herein in its entirety.

Such inhalation devices make use of a pumping unit having a pumping chamber formed by a hollow cylinder, into which a movable hollow piston can be inserted in order to reduce the internal volume of the chamber, thus increasing the pressure in the chamber and the pressure inside the piston, eventually resulting in the atomization of the liquid from the nozzle. By subsequently withdrawing the piston from the chamber, its internal volume increases and the resulting pressure reduction results in withdrawing liquid from the reservoir to the chamber, so that a new nebulization cycle can be started.

In order to protect the reservoir, which is usually designed as a collapsible bag, from damage and to facilitate the exchange of an empty reservoir for a new reservoir, the reservoir is incorporated into a rigid cartridge. The cartridge may be inserted into and withdrawn from the interior of the housing, which provides a corresponding fluid-mechanical interface to mechanically secure the cartridge and connect it to a downstream arranged component.

For the collapsible bag to function properly, the pressure inside and outside the bag must be substantially the same. When liquid is withdrawn from the bag to fill the pumping chamber, the volume of the bag is correspondingly reduced. In order to avoid the formation of increasingly stronger negative pressures inside the cartridge, said cartridge must allow to compensate the aforementioned volume reduction. This is achieved by providing at least one vent hole which allows ambient air to flow into the cartridge when the bag is deflated.

On the other hand, after manufacture and filling, a considerable time may elapse before the cartridge is used for the first time. In practice, the shelf life is usually one year or even longer. During this time, the aforementioned ventilation holes lead to an exchange of gas between the inside and the outside of the cartridge. Said exchange is undesirable, since the liquid components that may evaporate through the bag can reach the outside, and the incoming air increases the process of such undesirable evaporation.

In document DE 19940713 a1, a "cartridge for liquids" is disclosed, which avoids these conflicting requirements by providing the cartridge with a membrane which initially closes a vent hole located at the bottom of the cartridge. When the cartridge is inserted into the housing, the membrane is pierced by the needle and thus permanently opened. Once drilled, the cartridge must be used up within a certain period of time.

A disadvantage of this solution is that the time period may be rather short. Thus, if the device is not used for a long time, the cartridge must be disposed of and replaced even if the bag is not empty.

Disclosure of Invention

In a first aspect, the invention provides a cartridge (1) for storing a medically active liquid (L) and for supplying it to a pumping unit of an inhalation device,

-the inhalation device comprises a housing, a pumping unit fluidly connectable with the cartridge (1), a holder (2) for the cartridge (1) and a nozzle fluidly connected downstream of the pumping unit,

-wherein the pumping unit is capable of generating a negative gauge pressure for withdrawing a medically active liquid (L) from the cartridge (1) into the pumping unit and a positive gauge pressure for pressing the liquid (L) from the pumping unit into and through the nozzle for nebulizing the liquid (L) when the pumping unit is fluidly connected to the cartridge (1),

-wherein the cartridge (1) comprises an outer container (3) enclosing a foldable inner bag (4) and a cap (5) capable of closing the container (3), the cap (5) further providing an openable access opening (6) to the inner bag (4),

-wherein further the container (3) of the cartridge (1) has at least one pressure compensation opening (7),

and wherein the pressure compensation opening (7) is located in an area (8) of the container (3) covered by the cap (5).

In a second aspect, the invention provides a holder (2) for a cartridge (1) of the first aspect of the invention, wherein the holder (2) is adapted to be releasably connected to the cartridge (1) by clamping a cap (5) of the cartridge.

In a third aspect, the invention provides an inhalation device for delivering a medically active liquid in aerosol form, the inhalation device comprising a cartridge (1) according to the first aspect of the invention and a holder (2) according to the second aspect of the invention for holding the cartridge.

In a further aspect, the invention provides a method for treating, stabilizing or preventing a pulmonary disease or condition by inhalation administration of a medically active liquid in aerosolized form to a patient in need thereof, wherein the medically active liquid in aerosolized form is generated by an inhalation device according to the third aspect of the invention and administered to the patient, and a method for providing pressure compensation to an interior of an outer container (3) of a cartridge (1) according to the first aspect of the invention, comprising a collapsible inner bag.

Object of the Invention

It is an object of the present invention to provide a cartridge for an inhalation device which avoids the disadvantages of the known art. In particular, the cartridge according to the invention should allow a longer storage time of the drilled cartridge when not in use.

Detailed Description

This object is solved by a cartridge for storing a medically active liquid and for supplying it to a pumping unit of an inhalation device,

the inhalation device comprises a housing, a pumping unit which can be fluidly connected with the cartridge, a holder for the cartridge and a nozzle fluidly connected downstream of the pumping unit,

-wherein, when the pumping unit is fluidly connected to the cartridge, the pumping unit is capable of generating a negative gauge pressure for withdrawing a medically active liquid from the cartridge into the pumping unit and is capable of generating a positive gauge pressure for pressing the liquid from the pumping unit into and through the nozzle for nebulizing the liquid,

-wherein the cartridge comprises an outer container enclosing a collapsible inner bag and a cap capable of closing the container, the cap further providing an openable access opening to the inner bag,

-wherein further the container of the cartridge has at least one pressure compensation opening and wherein the pressure compensation opening is located in an area of the container covered by the cap.

Furthermore, the object is solved by an inhalation device comprising a cartridge as described above and a holder for said cartridge, wherein said holder is adapted to be releasably connected to the cartridge by clamping a cap of said cartridge.

Specific and/or advantageous embodiments of the aspects of the invention are described in the respective dependent claims, the subsequent description and the drawings.

The terms "comprises," "comprising," and "including" and similar referents are to be construed in an open and inclusive sense as "including, but not limited to," in the description and claims, unless the context clearly dictates otherwise.

The cartridge according to the first aspect of the invention is for storing a medically active liquid and for its supply to a pumping unit of an inhalation device as described above, i.e. an inhalation device comprising a housing, a pumping unit connectable or in fluid connection with the cartridge, a holder for holding the cartridge inside the housing, and at least one nozzle fluidly connected downstream (in fluid connection) of the pumping unit.

The pumping unit is or may be fluidly connected to the cartridge and is capable of generating a negative gauge pressure to draw the medically active liquid from the cartridge into the pumping unit and a positive gauge pressure to force the liquid from the pumping unit into the at least one nozzle and through the at least one nozzle to atomize (or atomize) the liquid.

The cartridge comprises an outer container enclosing a collapsible inner bag and a cap capable of closing the container. In particular embodiments, the cap is capable of hermetically closing the container. The cap further provides an openable access opening to the inner bag, i.e. an opening allowing the interior of the bag to be in fluid connection or fluidly coupled with the pumping unit (or more precisely with the pumping chamber of the pumping unit). Typically, the cap and access opening are located at a downstream end of the cartridge, which is commonly referred to as the "top" of the cartridge, and is generally located opposite the upstream or "bottom" of the cartridge. It is clear, however, that not all spatial indications are represented in a limiting manner, since the inhalation device can be used in any orientation. However, for the sake of clarity, in the following it is assumed that the cartridge is inserted into the bottom of an upright housing of an inhalation device and that the at least one nozzle is located in the top region of the device.

Further, the container of the cartridge has at least one pressure compensation opening which serves as the aforementioned vent and connects the space between the outer container and the foldable inner bag to ensure that in case the foldable inner bag does not completely fill the inner cavity of the outer container of the cartridge, the pressure in this space corresponds to the pressure of the surrounding atmosphere. As used herein, the term "at least one pressure compensation opening" means that the cartridge has only one pressure compensation opening or has a plurality of pressure compensation openings, such as, 2 to about 10, or 2 to 8, or 2 to 6, or 2 to 5, or 2 to 4, or 2 or 3 pressure compensation openings. In a particular embodiment, the cartridge has only one pressure compensation opening. In a further embodiment, the cartridge has 2 pressure compensation openings.

In case there are multiple pressure compensation openings, such as 2 or 3 or 4 or 5, or 2 or 3, or only 2 pressure compensation openings, in particular embodiments these pressure compensation openings may be located at opposite or equally spaced positions of the cartridge to ensure a uniform pressure compensation within the interior of the cartridge. For example, the pressure compensating openings may preferably be positioned in a spaced or equally spaced manner along a circumference or circle around a main axis of symmetry of the cartridge (such axis of symmetry connecting the top and bottom of the cartridge).

Thus, by means of this opening, the internal pressure of the cartridge can be adjusted to ambient pressure by letting air flow into or out of the cartridge.

According to the invention, the pressure compensation opening is located in the area of the container covered by the cap. In other words, the pressure compensation opening is located within the area or surface area at the top or downstream end of the container, preferably covered by the cap when the cartridge is detached from the holder or inhaler, respectively.

In case a plurality of pressure compensating openings as described above are provided in the container, preferably all said openings are located within the area or surface area of the container at the top or downstream end of the container, preferably covered by the cap when the cartridge is separated from the holder or inhaler, respectively.

More specifically, said area or region of the container is covered by the surface of the cap facing the container when detached from the holder or inhalation device, as described in further detail below. Preferably, the covering is provided in an airtight manner.

In other words, although according to the state of the art the pressure compensation opening is located at the bottom of the cartridge and thus spaced apart from said cap, according to the invention, the pressure compensation opening is not only located close to the cap and in the top area of the cartridge, but also in a way that it is actually covered by said cap.

The position of the opening under the cap has important advantages, as will become apparent from the description that follows.

According to the invention, the cartridge may be separate from the rest of the device, or it may be mounted inside the device. Thus, there are two "states".

In the state in which the cartridge is separated from the holder, the pressure compensation opening is preferably covered by a cap in an airtight manner. In the state when the cartridge is connected to the holder, the pressure compensation opening is open to allow pressure compensation or equalization between the inner cavity of the cartridge and the surrounding atmosphere, while the pressure compensation opening and the surrounding area may still be covered with a cap to ensure protection of the pressure compensation opening and the surrounding area from outside contamination.

This means that when the cartridge is separated from the device (in particular from the holder), it is preferably not possible to exchange gas between the interior of the cartridge and its external environment, nor is it possible to have other forms of contamination of the inner cavity of the cartridge by external contaminants. In addition to this, even a drilled cartridge may remain intact for a longer time, since liquid that may evaporate from the bag cannot leave the interior of the cartridge. This prevents or reduces loss of liquid while protecting the environment from potentially harmful substances emanating from the equipment on which it is resting.

The pressure compensation opening is only opened when the cartridge is inserted into a specially designed corresponding holder, which is necessary to achieve proper functioning of the device by allowing pressure compensation between the surrounding atmosphere and the inner cavity of the cartridge.

It is clear that when the device is not used for a long time, the cartridge has to be removed from the device or at least from the holder to achieve the desired closing of the pressure compensation opening.

In a particular embodiment, the housing is designed such that the cartridge can be retained inside the housing even when the opening is closed (e.g. by separating it from the holder). Preferably, the state of connection or disconnection can be detected from the outside (i.e., without opening the case). This may be achieved by a simple window or an at least partially transparent housing allowing to detect the position of the cartridge relative to the holder.

In a further embodiment, at least the cap connection region or area of the cap and/or the outer container is made of a deformable material. Further, the cap or at least said area may be deformable such that an air gap is provided between the container facing surface of the cap and the cap facing surface of the outer container, thereby allowing air flow and pressure compensation between the inner cavity or interior of the cartridge and the surrounding atmosphere by gas exchange via the pressure compensation opening.

In other words, by applying mechanical force to the cap or said region and thus deforming it, the region initially (in the disassembled or separated state) closing the aforementioned opening is lifted from said opening and provides said air gap. It is clear that the air gap must provide access to the outside, either directly or indirectly. In other words, the air gap allows an exchange of gas between the interior of the cartridge and its external environment. An indirect access would e.g. only lift the cap in order to provide a bypass for e.g. a permanently existing channel that itself leads to the outside. When such additional channels or the like are not required, direct access is provided.

The expression "interior" as used herein in this context refers to the space between the outer wall of the bag and the inner wall of the container.

In particular embodiments, the deformable material is elastically deformable. Thus, after the aforementioned application of force is stopped, the original shape of the cap is automatically restored or restored. However, further embodiments with plastically deformable materials are also possible; in these cases, an active reaction force may be required to obtain the original shape of the cap.

In a preferred embodiment, the cap is deformable by a radial compressive force. This means that the cap can be deformed according to the invention, for example, by providing force vectors arranged circumferentially around the cap. According to one embodiment, in addition to a substantially uniform distribution of the "ring" of forces, a set of one, two, three or four vectors is generally sufficient to cause the desired deformation.

According to a further embodiment, the cap has at least one protrusion at its outer periphery, which at the connected state of the cartridge causes the cap to deform to provide said air gap. In other words, in these embodiments, the holder is designed such that when the cartridge is inserted, the inner wall of the holder presses on the at least one protrusion. The forces resulting from the mechanical contact cause the aforementioned deformations.

It is clear that instead of (or in addition to) said one or more outer protrusions of the cap, the outer part of the cap may be designed as a plane and that one or more inner protrusions are provided at the inner wall of the holder facing the cap.

It is also clear to the skilled person how to design the one or more protrusions in order to obtain the desired force or forces along the aforementioned vector or vectors. It is also clear that a circumferential ring of protrusions may be used instead of a single or multiple protrusions if circumferential forces are required. In one embodiment, the one or more protrusions or rings, respectively, also serve as mechanical clips for detachably fixing the cartridge in a predetermined connection position inside the holder.

As previously mentioned, in a preferred embodiment, the cap and/or the retainer have a plurality of equally spaced protrusions.

In a second aspect, the invention also relates to a holder for a cartridge as defined above in connection with the first aspect of the invention. According to this second aspect of the invention, the holder is adapted to be releasably connected to the cartridge by clamping its cap (i.e. by clamping the cap of the cartridge). In other words, the holder provides the possibility of serving as a temporary fixation of the cap and thus of the entire cartridge within the housing of the inhalation device. Such a holder may have further features. However, the holder must at least be adapted to mechanically hold the cartridge in place.

Depending on the specific configuration of the cap, the retainer preferably enables interaction with the aforementioned one or more protrusions in order to provide said deformation force.

According to another embodiment, the holder itself (instead of or in addition to the cap) is at least partly made of an elastic material and is deformed upon insertion of the cartridge, thus enabling the provision of said air gap as described above. The skilled person can apply or transfer the mechanism and the aforementioned embodiments in connection with one or more protrusions etc. to the holder without problems.

Further, according to the invention, by means of the connection of the holder with the cartridge as described above, an air gap may be provided. In particular, the holder must allow for the creation of mechanical forces upon insertion of the cartridge, which results in mechanical deformation of the cap, which in turn requires the provision of the aforementioned air gap.

In one embodiment, the retainer is configured to apply a compressive force (or forces) to the cap when the cap is connected to the retainer.

In another embodiment, the force may be a tensile force. Depending on the particular configuration, such forces may also be used to create or "open" the aforementioned air gap. However, compressive forces are advantageous because they are easier to generate and can be used to clamp the cap at the same time.

In a third aspect, the present invention provides an inhalation device for delivering a medically active liquid in aerosol form, the inhalation device being adapted to hold or contain a cartridge according to the first aspect of the invention and comprising a holder according to the second aspect of the invention for holding the cartridge. Furthermore, according to this aspect, the invention relates to an inhalation device for delivering a medically active liquid in aerosol form, comprising a cartridge according to the first aspect of the invention and a holder according to the second aspect of the invention for holding the cartridge.

It should be noted that in connection with this and subsequent aspects, all embodiments, preferred embodiments and combinations thereof as described above in connection with the first and/or second aspect of the invention apply accordingly.

The term "medically active liquid" as used herein is to be understood in a broad sense and in a specific embodiment refers to a liquid or liquid composition useful for the treatment, stabilization or prevention of a condition, disorder or disease, in particular a pulmonary condition, disorder or disease of an animal or human, preferably a human, which may be contained in a cartridge according to the first aspect of the invention and may thus be administered by an inhalation device according to the third aspect of the invention.

In particular embodiments, the "medically active liquid" may itself be a compound or a mixture of compounds. In other embodiments, the medically active liquid may be a solution, suspension or dispersion of the ingredient or active ingredient in a physiologically acceptable carrier or liquid. In further embodiments, the physiologically acceptable carrier liquid may be water or an aqueous mixture comprising water and one or more additional physiologically acceptable solvents (such as ethanol, propylene glycol or polyethylene glycol).

In particular embodiments, the term "medically active liquid" as used herein may refer to a medically active liquid in the form of a pharmaceutical composition comprising at least one Active Pharmaceutical Ingredient (API), more specifically, at least one inhalable active pharmaceutical ingredient. More specifically, such at least one inhalable active pharmaceutical ingredient may for example be selected from the group consisting of long-acting muscarinic antagonists (LAMA), long-acting beta agonists (LABA) and inhalable glucocorticoids (ICS), as well as analgesics and antidiabetic agents, alone or in combination with each other.

Examples of Long Acting Muscarinic Antagonists (LAMA) that may be included in the medically active liquids referred to herein include, but are not limited to, aclidinium, glycopyrrolate salts, such as glycopyrrolate, renfenacin, tolonium bromide, such as tiotropium bromide, umeclidinium bromide, oxitropium bromide, flutolonium bromide, ipratropium bromide, trospium chloride, tolterodine.

Examples of long-acting beta agonists (LABA) that may be included in the medically active liquids referred to herein include, but are not limited to, salbutamol, arformoterol, bambuterol, bitolterol, bromsalterol, carbuterol, clenbuterol, fenoterol, formoterol, hexenephrine, ibuterol, indacaterol, indometacrol, neoprenol, isoproterenol, levalbuterol, mabuterol, metribulodine, oxiranol, metaproterenol, pirbuterol, procaterol, reproterol, limiproterol, ritodrine, salmeterol, sotriol, sulfonglycerol, talamde, terbutaline, and terbutaline.

Examples of inhalable glucocorticoids (ICS) that may be included in the medically active liquids referred to herein include, but are not limited to, prednisolone, prednisone, butyl Cork propionate, fluocinolone, beclomethasone, triamcinolone acetonide, budesonide, fluticasone, mometasone, ciclesonide, rofecolone, dexamethasone, etiporol-dichloroacetamide, deflazacort, etiporol, loteprednol, RPR-106541, NS-126, ST-26.

Furthermore, the active pharmaceutical ingredient which may be comprised by the medically active liquid referred to herein may be selected from analgesics, such as opioid analgesics (e.g. morphine, fentanyl) or non-opioid analgesics (e.g. salicylic acid derivatives, e.g. acetylsalicylic acid) or cannabinoids (e.g. tetrahydrocannabinol), anti-diabetic agents, such as insulin.

The medically active liquid or liquid pharmaceutical composition which may be administered by the present inhalation device in nebulized or aerosolized form may comprise at least one active pharmaceutical ingredient as described above, but may also comprise a mixture of two or more active pharmaceutical ingredients which may be administered by inhalation.

The medically active liquid or pharmaceutical composition which may be administered by the inhalation device according to the present invention in nebulized or aerosolized form and which may thus be contained in the cartridge according to the first aspect of the present invention is preferably formulated into a composition suitable and suitable for inhalation use, in other words a composition which may be nebulized or aerosolized for inhalation and which is physiologically acceptable for inhalation by a subject.

The medically active liquid or pharmaceutical composition which may be administered by an inhalation device according to this aspect of the invention or contained in the cartridge of the invention may be in the form of a dispersion (e.g. a suspension having a liquid continuous phase and a solid dispersed phase) or in the form of a solution.

In a further embodiment, the medically active liquid or pharmaceutical composition as described above may optionally comprise, in addition to the one or more active pharmaceutical ingredients, one or more physiologically acceptable excipients suitable for inhalation use. Excipients that may be characterized in the composition may include, but are not limited to, one or more buffers to adjust or control the pH of the solution, salts, taste masking agents, surfactants, lipids, antioxidants, and cosolvents, which may be used to increase or improve solubility, such as ethanol or ethylene glycol.

In particular embodiments, the medically active liquid as described above may be substantially free of propellant.

In a further embodiment, the medically active liquid as described above may be an aqueous solution in which one or more active pharmaceutical ingredients as described above are dissolved and solubilized in a liquid carrier solution comprising water. Such an aqueous solution may optionally further comprise one or more excipients as described above.

In a further aspect, the present invention provides a method for treating, stabilizing or preventing a pulmonary disease or condition in a subject by inhalation administration of a medically active liquid in aerosolized form to the subject, wherein the medically active liquid in aerosolized form is generated and administered to the patient by an inhalation device according to the third aspect of the present invention comprising a cartridge according to the first aspect and a corresponding holder according to the second aspect of the present invention.

Furthermore, the present invention relates to the use of an inhalation device according to claim 10 for treating, stabilizing or preventing a pulmonary disease or disorder by inhalation administration of a medically active liquid in aerosolized form to a subject in need thereof, wherein the medically active liquid in aerosolized form is generated and administered to the subject by inhalation according to the third aspect of the invention, the inhalation device comprising a cartridge according to the first aspect and a corresponding holder according to the second aspect of the invention.

The subject may be an animal, particularly a warm-blooded animal, such as a mammal or a human, in need of such treatment.

Examples of such pulmonary diseases or conditions to be treated, stabilized or prevented include, but are not limited to, asthma and Chronic Obstructive Pulmonary Disease (COPD).

In a still further aspect, the invention also relates to a method for providing pressure compensation to the interior of an outer container of a cartridge, in particular of the first aspect of the invention, containing a collapsible inner bag. For the sake of simplicity, reference is made to the above definitions, and in particular to a cartridge having a cap which is deformable, in particular by a radial compression force, preferably by means of at least one protrusion on the outer circumference of the cap and/or on the inner circumference of the holder.

According to this aspect of the invention, initially, the pressure compensation opening is closed before connecting the cartridge to the holder as also defined above, and subsequently, when the cartridge is connected to the holder, an air gap is provided which allows equalizing the pressure of the interior of the containing bag with the ambient pressure via the pressure compensation opening. The air gap may be formed, for example, by mechanically deforming (i) a region of the outer container that includes the pressure compensation opening and/or (ii) a region of the cap that covers the compensation opening.

In other words, according to one embodiment, the outer container preferably comprises a region or area at the top or downstream end of the cap closed container in which the pressure compensation opening is located, as described in further detail above in connection with the cartridge of the first aspect of the invention. When this region is deformed, an air gap is provided between the region and the cap.

According to another embodiment, the cap provides an area covering the aforementioned compensation opening, which is still located in the container. By deforming the cap (rather than the container), an air gap is provided.

Of course, the two alternative embodiments can be combined with each other.

According to a specific embodiment, the mechanical deformation is achieved by applying a radial compressive force from the holder to the cap when connecting the cartridge to the holder. To avoid repetition, reference is made to the above description. Of course, other ways of causing deformation when a force is applied to the cap and/or container are possible.

According to a further specific embodiment, upon subsequent removal of the cartridge from the holder, the mechanical deformation is reversed, so that the air gap is closed and the compensation opening is again (in particular in an air-tight manner) covered by the cap.

The advantages of the method according to this aspect of the invention are evident: the pressure compensation opening is only opened when an air gap is provided, which is the case only when the cartridge is inserted into the holder. Thus, when not in use, the cartridge can be removed, the pressure compensation opening closed, and no (undesired and unnecessary) exchange of air between the interior and the exterior of the container is possible.

The following list of numbered items is an embodiment encompassed by the present invention:

1. a cartridge (1) for storing a medically active liquid (L) and for supplying it to a pumping unit of an inhalation device,

-wherein further the container (3) of the cartridge (1) has a pressure compensating opening (7),

and wherein the pressure compensation opening (7) is located in an area of the container (8) covered by the cap (5).

2. The cartridge (1) according to claim 1, wherein the pressure compensation opening (7) is hermetically covered by the cap (5) in a state when the cartridge (1) is detached from the holder (2), and the pressure compensation opening (7) is opened in a state when the cartridge (1) is connected to the holder (2).

3. The cartridge (1) according to

item

1 or 2, wherein at least a cap connection area of the cap (5) and/or the outer container (3) is made of a deformable material and is deformable such that an air gap (9) is provided between an inner surface of the cap (5) and an outer surface of the outer container (3) facing the cap.

4. The cartridge (1) according to item 3, wherein the cap (5) is deformable by a radial compression force (F).

5. The cartridge (1) according to item 4, wherein at the outer circumference of the cap (5) and/or at the inner circumference of the holder (2) there is at least one protrusion (11) which in the connected state of the cartridge (1) causes a deformation of the cap (5) in order to provide the air gap (9).

6. The cartridge (1) according to claim 5, wherein the cap (5) and/or the holder (2) has a plurality of equally spaced protrusions (11).

7. Holder (2) for a cartridge (1) according to any of the preceding claims, wherein the holder (2) is adapted to be releasably connected to the cartridge (1) by clamping a cap (5) of the cartridge.

8. Holder (2) according to claim 7, wherein the air gap (9) may be provided by means of a connection of the holder (2) with a cartridge (1) according to claims 3 to 5.

9. The holder (2) according to claim 8, wherein the holder (2) is configured to apply a compressive force (F) onto the cap (5) when the cap (5) is connected to the holder (2).

10. Method for providing pressure compensation to the interior of the outer container (3) of a cartridge (1) according to any of the claims 3 to 6, containing the collapsible inner bag, wherein initially the pressure compensation opening (7) is closed before the cartridge (1) is connected to a holder (2) according to any of the claims 7 to 9, and wherein subsequently when the cartridge (1) is connected to the holder (2) an air gap (9) is provided which allows pressure equalization of the interior of the containing bag from the ambient pressure by means of mechanically deforming (i) the area of the outer container (3) comprising the pressure compensation opening and/or (ii) the area of the cap (5) covering the compensation opening.

11. Method according to item 10, wherein the mechanical deformation is achieved by applying a radial compression force (F) from the holder (2) to the cap (5) when connecting the cartridge (1) to the holder (2).

12. Method according to

item

10 or 11, wherein, upon subsequent detachment of the cartridge (1) from the holder (2), the mechanical deformation is reversed, so that the air gap (9) is closed and the compensation opening (7) is again hermetically covered by the cap (5).

13. An inhalation device for delivering a medically active liquid in the form of an aerosol, the inhalation device being adapted to hold or accommodate a cartridge according to any of items 1 to 6 and comprising a holder according to any of items 7 to 9 for holding the cartridge.

14. An inhalation device for delivering a medically active liquid in the form of an aerosol, comprising a cartridge (1) according to any one of claims 1 to 6 and a holder (2) according to any one of claims 7 to 9 for holding the cartridge.

15. A method for treating, stabilizing or preventing a pulmonary disease or disorder by inhalation administration of a medically active liquid in aerosolized form to a subject in need thereof, wherein the medically active liquid in aerosolized form is generated by an inhalation device according to item 13 or 14 and administered to the subject, the inhalation device comprising a cartridge (1) according to any one of items 1 to 6 and a holder (2) according to any one of items 7 to 9 for the cartridge.

16. Use of an inhalation device according to claim 13 or 14 for treating, stabilizing or preventing a pulmonary disease or disorder in a subject by inhalation administration of a medically active liquid in aerosolized form to the subject in need thereof, wherein the medically active liquid in aerosolized form is generated by an inhalation device according to claim 13 or 14 and administered to the subject, the inhalation device comprising a cartridge (1) according to any one of claims 1 to 6 and a holder (2) according to any one of claims 7 to 9 for the cartridge.

Detailed description of the drawings

Fig.1 shows a schematic cross-sectional view of a cartridge according to the invention in a detached state;

fig.2 shows this cartridge in a connected state;

fig.3 shows an embodiment of the cartridge with the cap removed from the container;

FIG.4 shows this embodiment with two components attached;

figure 5 shows the cartridge detached from the holder; and

fig.6 shows a sectional view of a detail of the cartridge according to fig. 5.

In fig.1 a schematic cross-sectional view of a cartridge 1 according to the invention in a detached state is shown. This is the case when the cartridge 1 is detached from the inhalation device.

The cartridge 1 comprises a foldable inner bag 4, which is surrounded by the container 3. The access opening 6, sealed by the lid 10, is located in the top (or downstream) region of the container 3, thereby providing (when opened) access to the interior of the bag 4 where the medically active liquid L is present.

At the shoulder of the container 3, there are two pressure compensation openings 7. Two pressure compensation openings 7 are located in an area 8 covered (or possibly covered) by the cap 5 and on opposite sides of the container 3. These openings 7 may provide for the connection of the inside of the container 3 (but not of the bag 4) to the outside. As can be seen from fig.1, the cap 5 closes the opening 7 in an airtight manner.

As can be seen from fig.2, which depicts the cartridge 1 in a connected state (holder not shown), the cap 5 is deformed by a radially acting compression force F. Furthermore, the seal 10 is broken so that the liquid L can pass through the access opening 6.

Due to the deformation, there is no longer a gas-tight closure of the pressure-compensating openings 7 by means of a cap, and an air gap 9 is provided at each opening 7. Thus, pressure compensation between the inside and the outside of the container 3 becomes possible. If the volume of the bag 4 is reduced due to a reduction in the amount of liquid L in the inner bag 4 as a result of continued use of the apparatus, the pressure difference generated between the interior of the container 3 and the exterior space can be effectively compensated for.

Fig.3 shows an embodiment of the cartridge 1, wherein the cap 5 is detached from the container 3. The access opening 6 is designed as a long hollow tube which can protrude into the almost invisible collapsible bag 4 when the cap 5 is attached to the container 3.

On the periphery of the outer part of the cap 5 there are protrusions 11. If a force acts on these protrusions 11, the cap 5 is deformed in such a way that an air gap (not visible) is provided, which allows the interior of the container 3 to be fluidly connected with the exterior through the pressure compensation opening 7. This deformation is reversible so that when the force is removed, the opening 7 closes again. In order to allow the opening 7 to be closed by the cap 5, the opening is arranged in an area 8 which is (or can be) covered by the cap 5.

As can also be seen in fig.3, the cap 5 is fixed to the container 3 by means of a clip closure. Corresponding geometrical features are present at the top end of the container 3 and inside the top end of the cap 5. If a suitable material is chosen for the cap 5, which material is preferably elastically deformable, no additional sealing or the like is required to provide a gas-and liquid-tight closure for the interface of the cap 5 with the container 3, and the interface of the interior of the cap 5 and the aforementioned region 8 in which the pressure-compensating opening 7 is located. This results in a simple arrangement requiring a minimum number of components.

The attachment member of fig.3 can be seen in fig. 4. The assembled cartridge 1 can be easily inserted into a holder (not shown), but can also be left for later use. When detached from the holder, the pressure compensation opening or openings (not visible) are closed in order to interrupt any gas exchange between the interior and the exterior of the container 3.

In fig.5, the cartridge 1 is depicted detached from the holder 2. As can be seen, the holder 2 is designed to clamp the cartridge 1 by means of a cap 5. The protrusions 11 fit in corresponding recesses 12 designed to inhibit rotation of the inserted cartridge 1 and to apply a compressive force (not shown) onto said protrusions 11, so as to provide an air gap (not shown) when the holder 2 holds the cartridge 1. The opening 7 is located in the "neck" region of the cartridge; however, it may also be located in the "shoulder" region as depicted in fig. 3.

Fig.6 shows a detailed cross-sectional view of the cartridge 1 and the holder 2. In this figure, the cap 5 is attached to the holder 2. A force (not shown) applies pressure to the protrusions 11 (one shown). By deformation of the cap 5, its inner surface is partially spaced from the opening 7, thereby providing an air gap (not shown) to compensate for pressure into the container 3 (bag 4 not shown).

List of reference numerals:

1 Cartridge

2 holder

3 Container

4 foldable inner bag

5 Cap

6 entry opening

7 pressure compensating opening

8 region

9 air gap

10 cover

11 protrusion

12 recess

L liquid

F, force.

Claims

and wherein the at least one pressure compensation opening (7) is located in a region (8) of the container (3) covered by the cap (5).

2. The cartridge (1) according to claim 1, wherein in a state when the cartridge (1) is detached from the holder (2) the at least one pressure compensation opening (7) is covered by the cap (5), and in a state when the cartridge (1) is connected to the holder (2) the pressure compensation opening (7) is open.

3. The cartridge according to claim 2, wherein the at least one pressure compensation opening (7) is hermetically covered by the cap (5) in a state when the cartridge (1) is separated from the holder (2).

4. The cartridge (1) according to any one of claims 1 to 3, wherein at least a cap connection area of the cap (5) and/or the outer container (3) is made of a deformable material and is deformable such that an air gap (9) is provided between an inner surface of the cap (5) and an outer surface of the outer container (3) facing the cap.

5. The cartridge (1) according to claim 4, wherein the cap (5) is deformable by a radial compression force (F).

6. The cartridge (1) according to claim 4 or 5, wherein at the outer circumference of the cap (5) and/or at the inner circumference of the holder (2) there is at least one protrusion (11) which in the connected state of the cartridge (1) causes a deformation of the cap (5) in order to provide the air gap (9).

7. The cartridge (1) according to claim 6, wherein the cap (5) and/or the holder (2) has a plurality of equally spaced protrusions (11).

8. The cartridge according to any one of claims 1 to 7, wherein the container (3) of the cartridge (1) has a plurality of pressure compensation openings (7).

9. The cartridge according to any one of claims 1 to 8, wherein the container (3) of the cartridge (1) has two pressure compensation openings (7).

10. Holder (2) for a cartridge (1) according to any of the preceding claims, wherein the holder (2) is adapted to be releasably connected to the cartridge (1) by clamping a cap (5) of the cartridge.

11. Holder (2) according to claim 10, wherein the air gap (9) can be provided by means of a connection of the holder (2) with a cartridge (1) according to claims 4 to 9.

12. The holder (2) according to claim 11, wherein the holder (2) is configured to apply a compressive force (F) onto the cap (5) when the cap (5) is connected to the holder (2).

13. An inhalation device for delivering a medically active liquid in the form of an aerosol, the inhalation device being adapted to hold or accommodate a cartridge according to any of claims 1 to 9 and comprising a holder according to any of claims 10 to 12 for holding the cartridge.

14. Inhalation device according to claim 13 for delivering a medically active liquid in aerosol form, comprising a cartridge (1) according to any of claims 1 to 9 and a holder (2) according to any of claims 10 to 12 for holding the cartridge.

15. Method for providing pressure compensation to the interior of the outer container (3) of a cartridge (1) according to any of claims 4 to 9 containing the collapsible inner bag, wherein initially the pressure compensation opening (7) is closed before the cartridge (1) is connected to the holder (2) according to any of claims 10 to 12, and wherein subsequently when the cartridge (1) is connected to the holder (2) an air gap (9) is provided which allows pressure equalization of the interior containing bag from the ambient pressure by means of mechanically deforming (i) the area of the outer container (3) comprising the pressure compensation opening and/or (ii) the area of the cap (5) covering the pressure compensation opening.

16. Method according to claim 15, wherein the mechanical deformation is achieved by applying a radial compression force (F) from the holder (2) to the cap (5) when connecting the cartridge (1) to the holder (2).

17. Method according to claims 15 to 16, wherein upon subsequent removal of the cartridge (1) from the holder (2), the mechanical deformation is reversed such that the air gap (9) is closed and the compensation opening (7) is again hermetically covered by the cap (5).

18. Use of an inhalation device according to claim 14 for treating, stabilizing or preventing a pulmonary disease or disorder in a subject by inhalation administration of a medically active liquid in aerosolized form to the subject in need thereof, wherein the medically active liquid in aerosolized form is generated and administered to the subject by the inhalation device according to claim 14, the inhalation device comprising a cartridge (1) according to any one of claims 1 to 9 and a holder (2) according to any one of claims 10 to 12 for the cartridge.